title: Reduction in SIV replication in rhesus macaques infused with autologous lymphocytes engineered with antiviral genes.
abstract: Simian immunodeficiency virus (SIV) infection of nonhuman primates is one of the most relevant animals models of HIV infection in humans. To test a potential anti-HIV gene therapy strategy in this model, CD4-enriched lymphocytes from three rhesus macaques were subjected to retrovirally mediated gene transfer with a vector expressing an antisense tat/rev gene. This group of animals and three control macaques were subsequently infected with SIVmac239. Blood and lymph nodes from all macaques were sampled for more than a year to monitor the progress of infection. Although all animals became infected, the animals that received the lymphocytes engineered with the antisense vector demonstrated a significant reduction in viral load in both peripheral blood and lymph nodes, had sustained numbers of CD4+ cells, and exhibited little disruption of lymph node architecture.
authors.affiliation: Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Rockville, Maryland 20901, USA.
authors.forename: R E
authors.initials: RE
authors.lastname: Donahue
authors.forename: B A
authors.initials: BA
authors.lastname: Bunnell
authors.forename: M C
authors.initials: MC
authors.lastname: Zink
authors.forename: M E
authors.initials: ME
authors.lastname: Metzger
authors.forename: R P
authors.initials: RP
authors.lastname: Westro
authors.forename: M R
authors.initials: MR
authors.lastname: Kirby
authors.forename: T
authors.initials: T
authors.lastname: Unangst
authors.forename: J E
authors.initials: JE
authors.lastname: Clements
authors.forename: R A
authors.initials: RA
authors.lastname: Morgan
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000821:virology*; D015694:Gene Products, rev; D015696:Gene Products, tat; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000494:pharmacology*; D008198:Lymph Nodes / Q000821:virology; D008253:Macaca mulatta / Q000821:virology*; D016376:Oligonucleotides, Antisense / Q000235:genetics; D016097:Simian Acquired Immunodeficiency Syndrome / Q000235:genetics / Q000628:therapy; D015302:Simian Immunodeficiency Virus / Q000235:genetics*; D014779:Virus Replication / Q000187:drug effects* / Q000235:genetics
chemical_list: D000998:Antiviral Agents; D015694:Gene Products, rev; D015696:Gene Products, tat; D016376:Oligonucleotides, Antisense